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Abstract :
[en] Exposure to parasitic helminths can imprint the immune system to modulate bystander immune responses to viral infection. We have recently shown that IL-4 induced during helminth infection expand bystander “virtual” memory CD8+ T cells (TVM) that results in enhanced control of murid gammaherpesvirus 4 (MuHV-4) lytic infection in the lung (Rolot et al., 2018. Nat Commun. 2018 Oct 30;9(1):4516). Whereas the frequency of TVM in secondary lymphoid organs in homeostasis is known to be higher in Balb/c compared to C57BL/6 mice, we observed here that IL-4c treatment or helminth exposure induced TVM expansion and enhanced CD8-mediated control of MuHV-4 in both strains. However, lung exposure to helminths in C57BL/6 mice resulted in severely increased viral loads after MuHV-4 infection. Such increased susceptibility to MuHV-4 infection was restricted to the strain C57BL/6 and was observed after induction of Schistosoma mansoni egg-induced lung inflammation and after Nippostrongylus brasiliensis infection. Following viral respiratory infection, MuHV-4 virions are first licensed by lung macrophages to infect alveolar epithelial cells, suggesting that macrophage responses could be affected by helminth-induced inflammation. Interestingly, helminth exposure induced a severe expansion of CD11b+ interstitial macrophages displaying M(IL-4) polarisation with increased Relm-α, PD-L2 and MHC-II expression. In addition, we observed increased proportions of MuHV-4-infected macrophages when C57BL/6 mice were exposed to helminths. Altogether, these results suggest that helminth infection affects the lung macrophages which become more permissive to MuHV-4 infection.